Sympathetic overactivity and coronary risk in hypertension
The authoritative meta-analysis of large antihypertensive trials by Collins et al. shows that antihypertensive therapy is fully capable of reducing strokes but that the effect on reduction of coronary events is less than anticipated. The failure to reduce coronary outcomes is particularly clear in younger patients.
To a student of physiology, such an outcome is not at all surprising because elevation of blood pressure is only one of multiple pathophysiologic abnormalities in hypertension. Many of these abnormalities are in their own right and independently of blood pressure are conducive to excessive coronary events. The interaction between the overactivity of the renin-angiotensin system and the sympathetic nervous system is one of the most important pressure-independent coronary risk factors in hypertension.
Trophic Effects
Both the renin-angiotensin system and the sympathetic nervous system favor cardiac and vascular hypertrophy. Whereas hypertrophy in the short term enhances the functional performance of cardiovascular organs, long-standing and advanced hypertrophy carries negative prognostic implications. A hypertrophic heart becomes stiffer, which impedes the diastolic filling and function. In due course the hypertrophic myocardium outgrows its blood supply, which eventually causes ischemic heart disease. It is therefore not surprising that left ventricular hypertrophy is an independent potent predictor of cardiovascular mortality.
As indicated earlier, hypertrophic arterioles become hyperresponsive and this leads to acceleration of hypertension. Because of the thicker wall, the hypertrophic vessels are also less capable of vasodilation. The insufficient vasodilation is further aggravated by pressure-related endothelial dysfunction. These processes lead to a substantial decrease in coronary reserve in hypertension.
Tachycardia
It is generally assumed that tachycardia is a benign sign, which is typical for nervous people whose blood pressure is only temporarily elevated. However, epidemiologic data do not provide support for such an interpretation. A fast heart rate is a strong and independent predictor of cardiovascular mortality and morbidity. The importance of heart rate could be predicted from physiology; the work of the heart is a product of both heart rate and blood pressure. Furthermore, the excessive and frequent pulsatile flow has a deleterious effect on coronary blood vessels and tachycardia is conducive to arrhythmias. Support for these statements can be found in a recent review.
Procoagulant Properties
Hypertension is frequently associated with elevated hematocrit values. High hematocrit, possibly because it increases the viscosity of blood, is a predictor of coronary mortality. The red blood cell volume in hypertension is normal and the high hematocrit is owing to a decrease in plasma volume. The decreased plasma volume in hypertension can be best explained by an increase in the capillary pressure, which causes a translocation of a small amount of plasma from the intravascular to the interstitial space. It is likely that one of the factors that increases the capillary pressure in hypertension is an excessive postcapillary a-adrenergic venoconstriction. In healthy humans, an infusion of sympathomimetic amines or an unopposed a-adrenergic tone causes a quick decrease in plasma volume. Furthermore, an association of indices of higher sympathetic tone with higher hematocrit values has been found in the Tecumseh epidemiologic study.
In addition to elevated hematocrit, an increased sympathetic tone (reflected in higher epinephrine values) has also been associated with signs of platelet overactivity in hypertension. Infusion of angiotensin II increases plasma fibrinogen inhibitor levels, which impedes fibrinolysis. Unfortunately, measurements of platelet overactivity and plasma fibrinolysis are not simple and their value as predictors of coronary risk has not been tested in epidemiologic studies. It stands to reason, however, that akin to high hematocrit, these procoagulant abnormalities may be conducive to excessive coronary thrombosis.
Insulin Resistance and Metabolic Syndrome
An elevated fasting plasma insulin is a sign of insulin resistance, a condition in which the insulin-mediated glucose uptake decreases. In such resistant individuals, higher insulin levels are needed to maintain normal blood glucose levels. Insulin resistance is intimately associated with dyslipidemia. An elevated plasma insulin level, independent of dyslipidemia, is a strong coronary risk factor.
High plasma insulin levels have been frequently found in hypertension. It has been proposed and experimentally verified that that a-adrenergic vasoconstriction may cause insulin resistance. In short, most of the insulin-mediated glucose uptake occurs in skeletal muscle cells. a-Adrenergic vasoconstriction decreases the nutritional blood flow to skeletal muscles and thereby impedes the glucose uptake by metabolically active myocites. Because less glucose is cleared, the pancreatic secretion of insulin increases in order to enhance the glucose clearance. The end result is a steady state of high insulin and near normal glucose. Support for this concept has been described in detail elsewhere and is based on the following observations. First, a decreased skeletal muscle capillary density has been found in insulin-resistant states of hypertension, obesity, and type II diabetes. Second, antihypertensive drugs that cause vasoconstriction worsen insulin resistance and those that cause vasodilation improve insulin sensitivity. Third, exercise training improves insulin sensitivity and increases skeletal muscle capillary density.
This post has been viewed 350 times.
Comments are closed.
